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Insights into the dynamics of ligand-induced dimerisation via mathematical modelling and analysis

White, Carla; Rottschäfer, Vivi; Bridge, Lloyd

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Authors

Carla White

Vivi Rottschäfer

Lloyd Bridge Lloyd.Bridge@uwe.ac.uk
Senior Lecturer in Mathematics



Abstract

The vascular endothelial growth factor (VEGF) receptor (VEGFR) system plays a role in cancer and many other diseases. It is widely accepted that VEGFR receptors dimerise in response to VEGF binding. However, analysis of these mechanisms and their implications for drug development still requires further exploration. In this paper, we present a mathematical model representing the binding of VEGF to VEGFR and the subsequent ligand-induced dimerisation. A key factor in this work is the qualitative and quantitative effect of binding cooperativity, which describes the effect that the binding of a ligand to a receptor has on the binding of that ligand to a second receptor, and the dimerisation of these receptors. We analyse the ordinary differential equation system at equilibrium, giving analytical solutions for the total amount of ligand bound. For time-course dynamics, we use numerical methods to explore possible behaviours under various parameter regimes, while perturbation analysis is used to understand the intricacies of these behaviours. Our simulation results show an excellent fit to experimental data, towards validating the model.

Citation

White, C., Rottschäfer, V., & Bridge, L. (2022). Insights into the dynamics of ligand-induced dimerisation via mathematical modelling and analysis. Journal of Theoretical Biology, 538, 110996. https://doi.org/10.1016/j.jtbi.2021.110996

Journal Article Type Article
Acceptance Date Dec 20, 2021
Online Publication Date Jan 24, 2022
Publication Date Apr 7, 2022
Deposit Date Feb 15, 2022
Publicly Available Date Mar 28, 2024
Journal Journal of Theoretical Biology
Print ISSN 0022-5193
Electronic ISSN 1095-8541
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 538
Pages 110996
DOI https://doi.org/10.1016/j.jtbi.2021.110996
Keywords Applied Mathematics; General Agricultural and Biological Sciences; General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; Modeling and Simulation; General Medicine; Statistics and Probability
Public URL https://uwe-repository.worktribe.com/output/9016395
Additional Information This article is maintained by: Elsevier; Article Title: Insights into the dynamics of ligand-induced dimerisation via mathematical modelling and analysis; Journal Title: Journal of Theoretical Biology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jtbi.2021.110996; Content Type: article; Copyright: © 2021 The Author(s). Published by Elsevier Ltd.

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